(2-hydroxy-3-(polychlorophenoxy)propyl)amine compounds



United States Patent ()flice Int. Cl. C07C 93/06 U.S. Cl. 260570.7 3 Claims ABSTRACT OF THE DISCLOSURE The present invention is directed to (fi-hydroxy-wphenoxyalkyl)guanidine compounds of the formula -R" NH cH-rm-e-lm This is a division of application, Ser. No. 643,032, filed June 2, 1967 now U.S. Pat. No. 3,437,691.

These products of the present invention are useful as agents to control the behavior of animals and are especially useful as hypotensive agents.

The present invention is also directed to preferred starting materials of the formula wherein x represents an integer of from 2 to 3, both inclusive; furthermore, the present invention is directed to other compounds which are the corresponding secondary amines of the above starting materials. These other compounds are of the following formula c11 an on Nlt Thus, these starting materials and corresponding secondary amines, expressed generically, are of the following formula wherein q represents an integer of from 1 to 2, both inclusive. The compounds of this formula, as the final products of the present invention, can be employed as agents 3H CH CH 0H NH to study and control the behavior of animals; in addition,

3,542,873 Patented Nov. 24, 1970 they are useful as agents to control the growth of plants, especially bacteria and fungi.

CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation-in-part of application Ser. No. 629,416, filed Apr. 19, 1967 and now abandoned for (p-Hydroxy-w-Phenoxyalkyl)Guanidine Compounds.

DETAILED DESCRIPTION OF THE INVENTION As set forth hereinabove, the present invention is directed to (B-hydroxy-w-phenoxyalkl)guanidine compounds of the formula Bi 0(- mt -4 Cll cu NH c N112 and their pharmaceutically acceptable acid addition salts. In the foregoing and following formulae, R represents methyl, methoxy, bromo, or chloro; R represents R, amino, or hydroxy; R" represents hydrogen or methyl; 11 represents an integer of from 1 to 4, both inclusive; m represents an integer of from 0 to 3, both inclusive; n represents an integer of from 0 to 1, both inclusive; and the sum of m and n is an integer of from 0 to 3, both inclusive.

The products of the present invention are typically crystalline solids. They are prepared by reaction of a (,B- hydroxy-w-phenoxyalkyl)amine of the formula a, 04411 4 4! cu Nu with 2-methylpseudothiourea, a compound of the following formula:

The 2-methylpseudothiourea can be employed, in fact is preferably employed, as a pharmaceutically acceptable acid addition salt; in this instance, the resulting product of the present invention is obtained asnthe salt of the same pharmaceutically acceptable acid. Most conveniently, if the 2-methylpseudothiourea is employed in a salt form, the sulfate or hemisulfate is used.

The reaction of (fl-hydroxy-w-phenoxyalkyl)amine and 2-methylpseudothiourea is conveniently carried out in an inert liquid reaction medium; suitable such media include hydrocarbons and the loweralkanols. The amounts of the reactants employed are not critical, some of the desired product being obtained when employing the reactants in any amount. However, the reaction consumes the reactants in amounts representing equimolecular propor tions, and the use of such amounts is preferred for the most efiicient usage of starting materials. The reaction takes place under a wide range of temperatures, such as from 0 C. to the reflux temperature of the liquid reaction medium selected. When a salt of 2-methylpseudothiourea is used, the reaction is preferably carried out at reflux. When 2-methylpseudothiourea, itself, is used, lower temperatures within the range, such as room temperatures, are preferred.

The reaction goes forward readily upon the contacting of the reactants in the reaction temperature range, with the production of the desired product and of methanethiol byproduct. However, higher yields are obtained when the reaction mixture is permitted to stand for a period of time, essentially until the evolution of methanethiol has ceased or markedly diminished. The product is separated from the reaction mixture in conventional procedures. Most typically, the product is a crystalline solid, and can conveniently be separated by filtration or decantation. If desired, the separated product can be purified, similarly in conventional procedures and most frequently by recrystallization.

When the product obtained as a result of the reaction is in the form of a salt, such salt can be converted, by reaction with a base, into the corresponding free base product. Such free base product can then be reacted with a pharmaceutically acceptable acid to obtain the corresponding pharmaceutically acceptable acid addition salt product. The ratio of acid to free base in a salt product is not critical. Ratios of 2:1 or 1:1 (free basezacid) are common and preferred.

In an alternate procedure, the products of the present invention can be prepared by the reaction of the Q-hydroxy-w-phenoxyalkyl)amine compound, as defined hereinabove, with cyanamide or dicyandiamide, which substances have the following respective formulae:

This reaction results in the preparation of the product of the present invention in the free base form. As noted above, the salt form can be obtained by reaction of the free base with a pharmaceutically acceptable acid.

In this alternate method, good results are obtained when employing the reactants in amounts representing equimolecular proportions, when employing an inert liquid reaction medium of the sort above described, and when conducting the reaction at reflux. Separation and purification are carried out as hereinabove described.

The identity of the pharmaceutically acceptable acid is not critical. Representative and suitable such acids include the following: hydrochloric acid, hydrobromic acid, bydriodic acid, sulfuric acid, acetic acid, salicyclic aid, valeric acid, oleic acid, benzoic acid, lauric acid, boric acid, lactic acid, nitric acid, phosphoric acid, citric acid, uric acid, succinic acid, tartaric acid, maleic acid, malonic acid, fumaric acid, cinnamic acid, and the like.

The following examples illustrate the best mode for carrying out the present invention and will enable those skilled in the prior art to practice the present invention.

EXAMPLE 1 [2-hydroxy-3-(2,6-dichlorophenoxy)propyl] guanidine hemisulfate [2-hydroxy-3- 2,6-dichlorophenoxy) propyl] amine l 5 grams; 0.063 mole) and Z-methylpseudothiourea hemisulfate (8.85 grams; 0.063 mole) were mixed together with 40 milliliters of ethanol and the resulting mixture heated to reflux temperature. The reaction mixture was maintained at reflux for 2 hours, then permitted to cool to room temperature and concentrated by removal of ethanol under subatmospheric pressure. The resulting concentrated substance, a syrup, was recrystallized from Water. As a result of these operations, there Was obtained the desired [2-hydroxy-3- 2,6-dichlorophenoxy) propyl] guanidine hemisulfate product, a crystalline solid melting, with decomposition, at 209- C.

EXAMPLE 2 [2-hydroxy-3-(2,6=dichlorophenoxy) propyl] guanidine hemisulfate [2hydroxy-3-( 3,4-dichlorophenoxy)propyl] amine (14.8 grams; 0.063 mole) and 2-methylpseudothiourea hemisulfate (8.8 grams; 0.063 mole) were mixed in 40 milliliters of ethanol. The resulting reaction mixture was heated to reflux temperature and refluxed for 2 /2 hours. The reaction mixture was then permitted to cool to room temperature; as the cooling took place, the desired [2- hydroxy-3- (3 ,4-dichlorophenoxy propyl] guanidine hemisulfate product precipitated in the reaction mixture. It was separated by filtration and recrystallized from water. The product so obtained melted, with decomposition, at 203 C.

Other representative examples prepared in accordance with the procedures reported in Examples 1 and 2 are identified in the following table, in which the symbol M.P. is employed as an abbreviation of the term melting point and the symbol m.w." is employed as an abbreviation of the term molecular weight.

EXAMPLES 3-30 From (2-hydroxy-3-phenoxypropyl)amine and Z-methylpseudothiourea hemisulfate, (2-hydroxy-3-phenoxypropyl)guanidine hemisulfate, a White crystalline product melting at l33-5 C.

From [2 hydroxy-3-(m-chlorophenoxy)propyl]amine and 2-methylpseudothiourea hemisulfate, [2-hydroxy-3- (m-chlorophenoxy)propyl]guanidine hemisulfate product, m.w. of 292.7.

From [2 hydroxy-3-(o-bromophenoxy)propyl]amine and 2-methylpseudothiourea hemisulfate, [2-hydroxy-3- (o-bromophenoxy)propyl]guanidine hemisulfate product, m.w. of 337.2.

From [2-hydroxy 3 (2,6-dichlorophenoxy)propyl] amine and 2-methylpseudothiourea hemisulfate, [2-hydroxy-3-(2,6-dichlorophenoxy)propyl] guanidine hemisulfate, a white crystalline product, M.P. 221 C.

From [Z-hydroxy 3 (2,5-clichlorophenoxy)propyl] amine and 2-methylpseudothiourea hemisulfate, [2-hydroxy-3-(2,5-dichlorophenoxy)propyl] guanidine hemisulfate, m.w. of 327.2.

From [2-hydroxy-4-(2,6-dichlorophenoxy)butyl]amine and 2-methylpseudothiourea hemisulfate, [2-hydroxy-4- (2,6-dichlorophenoxy)butyl]guanidine hemisulfate, m.w. of 341.2.

From [2-hydroxy-3-(4-amino-2,6-dichlorophenoxy)propyl]amine and Z-methylpseudothiourea hemisulfate, [2- hydroxy-3-(4 amino-2,6-dichlorophenoxy)propyl] guanidine hemisulfate, m.w. of 342.2.

From [2 hydroxy-3-(4-hydroxy-2,6-dichlorophenoxy) propyl]amine and 2 methylpseudothiourea hemisulfate, [2 hydroxy 3 (4 hydroxy 2,6 dichlorophenoxy)- propyl]guanidine hemisulfate, m.w. of 327.2.

From [2 hydroxy-3-(2,6 dibromophenoxy)propyl]- amine and 2 methylpseudothiourea hemisulfate, [2-hydroxy 3 (2,6 dibromophenoxy)propyl]guanidine hemisulfate, m.w. of 416.1.

From [2 hydroxy 3 (6-chloro-o-tolyloxy)-propyl] amine and Z-methylpseudothiourea hemisulfate, [2 hydroxy 3 (6 chloro-o-tolyloxy)propyl] guanidine hemisulfate, a white crystalline product, M.P. 6 C.

From [2 hydroxy 3-(4-chloro-2,6-xyly1oxy)-propyl] amine and 2 methylpseudothiourea hemisulfate, [2-hydroxy 3 (4 chloro-2,6-xylyloxy)propyl]guanidine hemisulfate, m.w. of 320.8.

From [2 hydroxy 3 (2,4,6-trichlorophenoxy)- propyl]amine and 2-methylpseudothiourea hemisulfate, [2 hydroxy 3 (2,4,6 trichlorophenoxy)propyl] guanidine hemisulfate, a white crystalline substance, M.P. 215-6 C. (dec.).

From [2 hydroxy 3 (2,6 dichloro 4 tolyloxy)- propylJamine and 2-methylpseudothiourea hemisulfate, [2 hydroxy 3 (2,6 dichloro 4 tolyloxy)propyl] guanidine hemisulfate, m.w. of 341.2.

From [2 hydroxy 3 (p-methoxyphenoxy)propyl]- amine and 2 methylpseudothiourea hemisulfate, [2-hydroxy 3 (p methoxyphenoxy)propyl] guanidine hemisulfate, a white crystalline product, M.P. of 15860 C.

From [2 hydroxy 3 (3,4,5 trimethoxyphenoxy)- propyl]amine and 2 methylpseudothiourea hemisulfate, (2 hydroxy 3 (3,4,5-trimethoxyphenoxy)propyl] guanidine hemisulfate, m.w. of 348.3.

From [2 hydroxy 3 (2,6 xylyloxy)propyl] amine and 2 methylpseudothiourea hernisulfate, [2-hydroxy-3- (2,6 xylyloxy)propyl]guanidine hemisulfate, a white Crystalline product, M.P. 1823 C.

From [2 hydroxy 3 (2,4,6 trimethylphenoxy)- To the aqueous solution of the free base [2 hydroxy- 3 (2,6 dichlorophenoxy)propyl]guanidine prepared as described in Example 31 there is added an equimolecular amount of maleic acid. Thereafter, water is removed by evaporation under subatmospheric pressure to obtain the propyl]amine and Z-methylpseudothiourea hemisulfate, desired [2 hydroxy 3 (2,6-dichlorophenoxy)propyl] [2 hydroxy 3 (2,4,6 trimethylphenoxy)propyl] guanidine maleate, m.w. of 394. guanidine hemisulfate, m.w. of 300.3.

From [2 hydroxy 3 phenoxy 1 methylpropyl]- EXAMPLES 33 34 amine and 2-methylpseudothiourea hemisulfate, [2-hy- Y 3 PhenOXy 1 y p py lg hemi- Other salt and free base products of the present inven- Sulfate, 0f tion are similarly prepared. Such other products include From y y 4 P Y 1 y y lthe following representatives: (2-hydroxy-3-(o-chloroamine and 2 methylpseudothiourea hemislllfate, yphenoxy)propyl)guanidine (m.w. of 243.7) and the cordroxy 4 p y 1 y y ls i i iresponding hydrochloride (m.w. of 280.2); (2-hydroxy-3- Sulfate, of 2853- (6-chloro-2-tolyloxy)propyl)guanidine (m.w. of 257.7) From hy r xy 4 IP Y)- and its citrate (m.w. of 450); (2-hydroxy-3-(2,6-xy1yloxy) methylbutyllamine and 2 methylpseudothiourea hemipropyl)guanidine (m.w. of 237.3) and the corresponding sulfate, y y 4 p y) nitrate (m.w. of 300.3); (2-hydroxy-3-(2,4,6-trichloromethylbutyl]guanidine hemisulfate, m.w. of 355.2. phenoxy)propyl)guanidine (m.w. of 312.6) and the corre- Fr m [2 hy roxy 3 p Y)p py sponding phosphate (m.w. of 344.6); (2-hydroxy-3-(2,6- amine and 2-methylpseudothiourea hemisulfatc, [2 hydichlorophenoxy)-l-rnethyl-propyl)guanidine (m.w. of drOXY 3 P WP PYU guanidine hemi- 293) and the corresponding hydrobromide (m.w. of 373); sulfate, M.P. 1546 C. and (2-hydroxy-3-(2,6-dichlorophenoxy)hexyl)guanidine From, y xy 6 chl0rophenoxy)- (m.w. of 320.2) and the corresponding tartrate (m.w. of hexyl]amine and 2 methylpseudothiourea hemisulfate, 470,3). [2 hydroxy 6 (2,6 dichlorophenoxy)hexyl]guanidine The products of the present invention are useful for hemisulfate, m.w. of 369.2. studying and controlling the behavior of animals such as From (2 hydroxy 5 phenoxypentyl)amine and mice, rats, dogs, and monkeys. In particular, the products 2 methylpseudothiourea hemisulfate, (2 hydroxy 5- exhibit adrenergic neuron blocking activity and thus can phenoxypentyl)guanidine hemisulfate, m.w. of 286.3. be employed as hypotensive agents. They can also be used From [2 hydroxy 6 (p tolyloxy)hexyl]amine as antidepressants. and 2 methylpseudothiourea hemisulfate, (2 hydroxy- (2 hydroxy-3-(2,6-dichlorophenoxy)propyl)-guanidine 6-(p-tolyloxy)he'xyl] guanidine hemisulfate, m.w. of 314.4. hcmisulfate was evaluated in mice. In this evaluation, each From [2 hydroxy 5 (p-methoxyphenoxy)pentyl]- member of a group of mice was injected intraperitoneally amine and 2 methylpseudothiourea hemisulfate, [2-hywith reserpine at the rate of 5 milligrams per kilogram of droxy 5 (p-methoxyphenoxy)pentyl]guanidine hemianimal body weight, as a 0.05 percent aqueous solution. sulfate, m.w. of 316.3. Thereafter, the mice were held for a period of about 18 From [2 hydroxy 5 (4 bromo-o-tolyloxy)-1- to 24 hours; at this time, the (2-hydroxy-3-(2,6-dichloromethylpentyHamine and 2 methylpseudothiourea hemiphenoxy)propyl)-guanidine was administered, by intrasulfate, [2 hydroxy 5 (4 bromo-o-tolyloxy) 1- peritoneal injection at the rate of milligrams per kilomethylpentyl1guanidine hemisulfate, m.w. of 393.3. gram of animal body weight. The mice were thereafter ob- From [2 hydroxy 6 (p-aminophenoxy)hexyl] amine served for possible reversal of the symptoms of ptosis and and 2 methylpseudothiourea hemisulfate, [2 hydroxydepression caused by reserpine administration. It was oh- 6 (p aminophenoxy)hexyl] guanidine hemisulfate, 45 served that of 10 mice in the group, reserpine effects in 8 m.w. of 315.4. were reversed by administration of the subject compound.

Fr m [2 hydroxy 5 (4 hydroxy 2,6-di hl r In another evaluation, (2-hydroxy-3-(2,6-dichlorophephenoxy)pentyl]amine and 2 methylpseudothiourea Y)P PY W administered t an an s h i lfat 2 hydroxy 5 4 hydroxy 2 5 1 0 mod cat. Anesthesia was induced by intravenous adminisphenoxy)pentyl]guanidine hemisulfate, m.w. of 371.2. 5 tl'atlon 0f Pentobarbltal at the rate of 32 mllllgrams P kilogram of animal body weight. Thereafter, both the pre- EXAMPLE 31 ganglionic and post-ganglionic cervical nerves were iso- [2-hydroxy-3-(2,6-dichlorophenoxy)propyl]guanidine lated and bipolar silver electrodes positioned on each. Stimulation of the isolated nerves in the course of the aqueous Sohmon banum hydroxlde 18 added to evaluation was at a frequency of 29 pulses/ second for two a chilled aqueous solution of [2 hydroxy 3 (2,6-

milli-seconds at a voltage of 2 to 4 volts. The nictitating d1chlorophenoxy)propyl]guanidine hemisulfate prepared m,

embrane was linked to a force displacement transducer. as described in Example 1. The barium hydroxide and The (2 h ydroxy-3-(2,6-dichlorophenoxy)propyl)guanihemisulfate reactants are employed in equivalent amounts. d t d b tr h Addition of the barium hydroxide solution results in the me was a i f y m avenous mlectlfm m t e precipitation of barium sulfate, which is removed from P of 8 mllhgrams lillogram of ammal body the solution by filtration. The solution contains the de- Y Contractlon 9 E mcmatmg f sired free base, [2 hydroxy 3 (2,6 dichlorophenoxy) mg each of PFe -ga11g11 0I11C and po tg Stlm111at 10n propy1)guanidine It has a molecular weight f 27 2 was recorded ust prior to administration of the sub ect EXAMPLE 32 compound, immediately after administration of the subject compound, and at 1, 2, 3, and 4 hours following ad- [2-hydroxy-3-(2,6-dichlorophenoxy)propyl]guanidine ministration of the subject compound. The results are set maleate forth in the following table.

MILLIMETERS OF CONTRACTION 1 hour 2 hours 3 hours 4 hours Before Immediately after adafter adafter adafter adadminister adminisminismlnisministration ministration tration tration tration tration Pre'ganglionic stimulation 27 29 12. 5 4 4 2 Post-ganglionic stimulation 23 25 14 9 7 5 In the employment of the final products of the present invention for studying and controlling the behavior of animals, the unmodified compounds can be used. However, it is generally preferred to employ a composition comprising one or more of the products and one or more adjuvants which are pharmaceutically acceptable and facilitate the administration of the compound. For example, a product can be formulated in water, which can be a physiological saline solution. When a product is to be administered orally, it can be formulated in a tablet, animal feed, capsule, or the like, by techniques known in the art of formulation.

The final products of the present invention, in addition to being useful as agents for studying and controlling the behavior of animals, are useful as agents to control the growth of plants, especially bacteria and fungi. In this embodiment, there is employed one or more of the unmodified compounds, or, preferably, a suitable formulation containing one or more of the compounds and one or more adjuvants, such as surface active dispersing agents, liquid diluents, and the like. In representative operations, 2-hydroxy-3- 6-chloro-o-tolyloxy propyl guanidine hemisulfate was incorporated in a culture medium in the amount of 0.05 percent and the medium inoculated with Bacillus subtill's. Observations forty-eight hours later showed complete inhibition of the growth of the organism.

Those compounds to be used as starting materials in the preparation of the products of the present invention, which starting materials are of the following formula:

are prepared in known procedures. In these procedures, an epoxy compound of the formula is reacted with ammonia, conveniently supplied as ammonium hydroxide. Good results are obtained when reacting equimolecular proportions of the reactants in a loweralkanol as reaction medium and at reflux temperatures.

A preferred species of the present invention is the group of compounds designated by the following formula at on E p11 cu c11 ma and their pharmaceutically acceptable acid addition salts. In the above and succeeding formulae, x represents an 8 integer of from 2 to 3, both inclusive. Related to these compounds are the corresponding secondary amine compounds of the formula:

. on C o l cu cu 01: Nil 1 2 Thus, these starting materials and the corresponding secondary amines, expressed generically, are of the following formula:

fo I 9 i 3 o 011 --CH 0H wherein q represents an integer of from 1 to 2, both inclusive. As noted foregoing, these compounds, as the final products of the present invention, can be employed as agents to study and control the behavior of animals; in addition, they are useful as agents to control the growth of plants, particularly fungi and bacteria.

All of these compounds are prepared in a reaction which produces a mixture of both the primary amine starting material and its corresponding secondary amine. This reaction comprises the reaction of a 1,2-epoxy-3-phenoxypropane having the following formula:

with ammonia, which can be supplied as ammonium hydroxide. The reaction is conveniently carried out in a liquid reaction medium, the water of the ammonium hydroxide reactant typically serving this function. However, other organic solvents can be used and the ammonia bubbled into the reaction mixture. Also, even when the water of ammonium hydroxide serves as reaction medium, other solvents which are water-miscible, such as the loweralkanols, can be used in conjunction with the ammonium hydroxide. The exact amounts of the reactants employed are not critical, some of the desired primary amine product and corresponding secondary amine product being obtained regardless of the amounts. However, although the reactions of 1,2-epoxy-3-phenoxypropane and ammonium hydroxide consume the reactants in stoichiometric amounts, higher yields generally are obtained when employing an excess amount of the ammonium hydroxide. Thus, it is preferred to employ the reactants in amounts representing one molecular proportion of 1,2-epoxy-3- phenoxypropane and from one to ten or more molecular proportions of ammonium hydroxide.

The reaction goes forward readily under a wide range of temperatures, such as from 10 to 100 0.; generally, though, it is preferred to conduct it at temperatures of from 25 to C. As noted, the reaction results in the preparation of a mixture of the desired primary and secondary amines. They can be removed from the reaction mixture separately, or removed jointly and thereafter separated, in conventional procedures. Most typically, in separating the products, advantage is taken of the different solubilities of the primary and secondary amines in the reaction mixture. The separated products can thereafter be purified, if desired, in conventional procedures.

In carrying out the reaction, the 1,2-epoxy-3-phenoxypropane is reacted with ammonia, conveniently as ammonium hydroxide, and with additional solvent if desired, and the reaction mixture held in the reaction temperature range for a period of time. The secondary amine is typically separated and removed by filtration, and the reaction mixture thereafter subjected to evaporation under subatmospheric pressure to remove solvent and obtain the corresponding primary amine. As the products are typically crystalline solids, purification is readily achieved by recrystallization from suitable solvent.

In the preparation of the pharmaceutically acceptable acid addition salts of the preferred starting materials and corresponding secondary amines, the base is reacted with a pharmaceutically acceptable acid to obtain the corresponding salt product. The ratio of acid to free base in a salt product is not critical. Ratios of 1:1 are common and preferred. Representative pharmaceutically acceptable acids include those identified hereinabove as suitable for salt formation with the final products of the present invention.

The following examples further illustrate embodiments of the present invention in the preferred starting materials and the corresponding secondary amines, and will enable those skilled in the art to practice the same.

EXAMPLE 45 Preparation and separation of [2-hydroxy-3-(2,4-dichlorophenoxy)propy1]amine and bis[2 hydroxy-3-(2,4 dichlorophenoxy )propyl] amine 50 grams of 3-(2,4-dichlorophenoxy)-l,2-epoxypropane (0.228 mole) were added to a solution of 160 milliliters of ethanol and 193 milliliters of 28 percent ammonium hydroxide. The resulting reaction mixture was gradually heated to reflux and refluxed for 15 minutes. The reaction mixture was then cooled to 25 C. and filtered to separate the secondary amine, bis[2-hydroxy-3-(2,4-dichlorophen oxy)propyl] amine, M.P. 124-30 C., in a yield of 24 percent.

Reaction medium was removed from the filtrate by evaporation under subatmospheric pressure and residual water removed by azeotroping with benzene. As a result of these operations, the desired corresponding primary amine, [2-hydroxy-3-(2,4-dichlorophenoxy)propyl]amine, M.P. 7980 C., was obtained. The yield was 35 percent.

EXAMPLE 46 Preparation and separation of [2-hydroxy-3-(2,4,6-trichlorophenoxy)propyl] amine and bis[2 hydroxy 3- (2,4,6-trichlorophenoxy propyl] amine 3-(2,4,6 trichlorophenoxy) 1,2 epoxypropane (81.5 grams; 0.32 mole) was added to a mixture of 310.milliliters of ethanol and 240 milliliters of 28 percent ammonium hydroxide. The resulting mixture was heated to reflux temperature, refluxed for 15 minutes, and then cooled to room temperature. Cooling of the reaction mixture was accompanied by precipitation therein of a white crystalline substance, the desired secondary amine product, bis[2-hydroxy-3-(2,4,6-trichlorophenoxy)propyl]amine. It was separated by filtration and found to melt at l3l8 C. It was obtained in a 25 percent yield.

Thereafter, the filtrate was subjected to evaporation under subatmospheric pressure to obtain the corresponding primary amine, [2 hydroxy-3-(2,4,6 trichlorophenoxy) propyllamine. It was purified by recrystallization from benzene, the purified product melting at 1ll2 C. The amount of primary amine obtained represented a 44 percent yield.

EXAMPLE 47 [2-hydroxy-3- (2,4-dichlorophenoxy) propyl] amine maleate To the aqueous solution of the free base [2-hydroxy-3- (2,4-dichlorophenoxy)propyl] amine prepared as described in Example 45 there is added an equimolecular amount of maleic acid. Thereafter, water is removed by evaporation under subatmospheric pressure to obtain the desired [2-hydroxy-3-(2,4 dichlorophenoxy)propyl] amine maleate, having a molecular weight of 352.2.

EXAMPLE 48-57 Other representative products, prepared in accordance with the foregoing teachings and examples, include the following: [2 hydroxy-3-(2,3 dichlorophenoxy)propyl] amine, M.P. Ill-2 C.; bis[2-hydroxy-3-(2,3-dichlorophenoxy)propyl]amine, M.P. 126-3l C.; [2-hydroxy-3- (2,5 dichlorophenoxy)propyl] amine, M.P. 1234 C.; bis[2-hydroxy 3 (2,5 dichlorophenoxy)propyl]amine, M.P. 1528 C.; [2-hydroxy 3 (2,6 dichlorophenoxy) propyl] amine, M.P. 923 C.; bis [2-hydroxy-3-(2,6-dichlorophenoxy)propyl]amine, M.P. l325 C.; [2-hydroxy-3-(3,4-dichlorophenoxy)propyl]amine, M.P. 103- 6 C.; bis[2-hydroxy 3 (3,4 dichlorophenoxy)propyl] amine, M.P. 131-3 C.; [2-hydroxy-3-(2,4,5-trichlorophenoxy)propyl]amine, M.P. ll2-3 C.; and bis[2-hydroxy 3 (2,4,5 trichlorophenoxy)propyl]amine, M.P. 146-51 C.

EXAMPLES 5 864 Representative salt products include the following, the symbol m.w. being employed as an abbreviation for the term molecular weight: [2-hydroxy-3-(2,6-dichlorophenoxy)propyl]amine hydrochloride, m.w. of 272.5; bis[2 hydroxy 3 (2,5-dichlorophenoxy)propyl]amine acetate, m.w., 515.2; [2-hydroxy-3-(2,4,5-trichlorophenoxy)propyl]amine maleate, m.w. of 386.5; bis[2-hydroxy- 3 (2,4,6-trichlorophenoxy) propyl1amine hydrobromide, m.w., 605.0; [2-hydroxy-3-(2,4-dichlorophenoxy)propyl] amine nitrate, m.w. of 299; bis[2-hydroxy-3-(2,4-dichlorophenoxy)propyl]amine maleate, m.w., 571.3; and [2-hydroxy-3-(3,4-dichlorophenoxy)propyl] amine citrate, m.w. of 428.

The preferred starting materials and corresponding secondary amines, as noted foregoing, are useful as agents to control the growth of plants, particularly bacteria and fungi, such as, for example, Aerobacter aerogenes, Bacillus subtilis, Pseudomonas aeruginosa, Salmonella typhosa, Staphylococcus aureus, Aspergillus terreus, Candida pelliculosa, Pullulariw pullulans, and Rhizopus nigricans. In such application, the unmodified compounds can be used. Preferably, however, compositions comprising the compounds are employed. For example, the compounds can be dispersed on a finely divided solid and employed as dusts. Also, such mixtures can be dispersed in water with the aid of a wetting agent and the resulting aqueous suspensions employed as sprays. In other procedures, the products can be employed as constituents of organic liquid solutions, oil-in-water or water-in-oil emulsions or water dispersions with or without the addition of wetting, dispersing or emulsifying agents.

In representative operations, amounts of bis[2-hydroxy- 3-(3,4-dichlorophenoxy)propyl]amine and a standard microbiological culture medium were mixed together to obtain a test medium containing 0.05 percent by weight of the specified compound. This test medium and an unmodified portion of the same standard microbiological culture medium, the latter serving as a control, were inoculated with Bacillus subtilis, and the inoculated cultures thereafter held under conditions conducive to their growth. Observations at twenty-four and forty-eight hours following inoculation showed a complete inhibition of the growth of the organism in the test medium, whereas the control medium showed an abundant growth of the organisrn.

Essentially the same results were obtained with the following compounds:

[2-hydroxy-3 (2,5-dichlorophenoxy propyl] amine; [2-hydroxy-3 (2,4-dichlorophenoxy) pro pyl] amine; [2hydroxy-3 (2, 3-dichlo rophenoxy propyl] amine; [2-hydroxy-3 (2,4,5 -trichlorophenoxy propyl] amine; and [2-hydroxy-3 (2,4,6-trichlorophenoxy) propyl] amine.

I claim: References Cited 1. Compound Of the formula C1 OH 3,331,850 7/1967 Youngdale 260570.7 X

I o CH2 CH CH2 q 5 OTHER REFERENCES Merchant et 211.: Chemical Abstracts, vol. 55, p. (3"!) 19844 (1961).

and its pharmaceutically acceptable acid addition salts, ROBERT V. HINES,PrimaIY Examiner wherein x represents and q represents an integer of from 10 1 to 2, both inclusive. US. Cl. X.R.

2. The compound of claim 1 wherein q represents 2. 71 103, 121, 122, 124; 260 348, 501.14, 501.17, 564; 3. The compound of claim 1 wherein q represents 1. 424-326, 330 

